葛根素的多晶型研究

目的：解析不同晶态葛根素的理化性质变化。方法：采用4种不同溶剂进行结晶，应用显微放大、溶解度、红外、X射线衍射、热分析。结果：不同晶态的晶体在水中的溶解度随着晶型的增大而减小；热分析显示4种晶体的熔点存在差异；X射线衍射测得4种晶体的厚度不一样，特别是用乙醇水结晶的样品结晶度最低；红外谱图显示4种晶体有差异，并且超临界流体结晶所得样品和标准红外谱图一致。结论：不同晶态的葛根素其理化性质有明显差异。     

盐酸阿替卡因的多晶型研究

目的:建立盐酸阿替卡因多晶型的测定方法并研究其理化性质.方法:研究了不同晶型的盐酸阿替卡因的制备方法,采用熔点测定、差示扫描量热法(DSC)、红外吸收光谱法(IR)及粉末X-衍射法(Powder X-ray)研究了不同晶型的特征,并考察了2种晶型在高湿、高温和光照条件下的稳定性.结果:盐酸阿替卡因存在2种不同的晶型,晶型Ⅰ和晶型Ⅱ.通过熔点测定、DSC和IR分析及粉末X-衍射法可区分2种晶型.晶型Ⅰ有较强的吸湿性,而晶型Ⅱ不易吸湿,2种晶型对光照和高温均较稳定.结论:盐酸阿替卡的晶型Ⅱ适合作为药物应用.     

盐酸厄洛替尼晶型研究

目的：对盐酸厄洛替尼A晶型、B晶型进行鉴定,了解制剂过程对晶型稳定性的影响,确定A晶型盐酸厄洛替尼片的开发工艺。方法：通过X射线粉末衍射（XRD）、红外分光光度法（IR）、电镜扫描（SEM）和差式扫描量热分析（DSC）,对两种晶型进行鉴定。通过XRD技术对晶型的转化进行研究,并比较两种晶型的理化性质及片剂在溶出介质中的溶出行为差异,对片剂的工艺开发进行初步研究。结果：两种晶型具有不同的晶型特征。 A晶型溶解性好,溶出速度快,稳定性差;而B晶型具有较好的稳定性。湿法制粒中润湿剂的加入会导致A晶型转变为B晶型。结论：采用XRD、IR、SEM和DSC技术可以对药物晶型进行快速、准确的鉴定。以A晶型替代B晶型制备盐酸厄洛替尼片,采用干法制粒,但需改善包装,保证晶型的稳定性。     

头孢替唑钠的结晶性研究

目的探讨头孢替唑钠的结晶特性。方法利用单晶X射线衍射、粉末X射线衍射、DSC和TGA等理化分析方法,分析不同条件得到的头孢替唑钠晶体。结果头孢替唑钠晶体为头孢替唑钠一水合物,至少有I型和II型两种不同的晶型;水分子在不同的头孢替唑钠晶格中有不同的结合状态。结论不同结晶条件下得到的头孢替唑钠一水合物的晶格结构略有差异,并影响晶体的热稳定性。I型晶体较II型晶体对热稳定。     

阿戈美拉汀的多晶型研究

目的研究阿戈美拉汀的多晶型特征。方法通过平衡溶解度测定、差示扫描量热分析(DSC)、红外光谱(IR)、粉末X射线衍射(PXRD)谱等鉴定阿戈美拉汀多的晶型,并考察其室温放置的稳定性。结果获得Ⅰ～Ⅳ型阿戈美拉汀。利用DSC或PXRD分析可区分4种晶型。结论不同晶型阿戈美拉汀的理化性质有明显差异。Ⅱ型阿戈美拉汀最稳定,Ⅰ、Ⅲ、Ⅳ型稳定性较差。     

马来酸替加色罗的晶型研究

目的：研究马来酸替加色罗2种晶型的物理性质。方法：运用傅立叶变换红外光谱、拉曼光谱、热分析和粉末X-射线衍射法研究马来酸替加色罗的晶型。结果：运用不同的重结晶溶剂，马来酸替加色罗可形成2种晶型，这2种晶型的熔点一致，它们的DSC和TG曲线都相同。但他们的红外光谱、拉曼光谱和粉末X-射线衍射图谱均存在着差异。结论：红外光谱、拉曼光谱和粉末X-射线衍射图谱可作为鉴别马来酸替加色罗晶型的方法。     

盐酸阿替卡因的多晶型研究

目的研究局部麻醉药盐酸阿替卡因的多晶型及吸湿性.方法用熔点测定、差示扫描量热法(DSC),红外吸收光谱法(IR)及粉末X-衍射法(Powder X-ray)研究了盐酸阿替卡因不同晶型的特征.结果与结论证明盐酸阿替卡因存在两种不同的晶型,晶型Ⅰ和晶型Ⅱ.     

瑞巴派特新晶型分析及与溶出速率的关系

目的制备一种瑞巴派特球状结晶的新晶型并考察新晶型对瑞巴派特溶出速率的影响。方法以N,N-二甲基甲酰胺-乙酸乙酯重结晶法制备新晶型瑞巴派特球状晶体,通过扫描电镜法、红外吸收光谱法和X射线粉末衍射法对其进行结构分析;采用紫外-可见分光光度法考察其对在不同p H介质中的原料药溶出速率的影响。结果瑞巴派特针状晶体和球状晶体不仅晶体外观形状不同,且其红外吸收光谱图和X射线粉末衍射图谱都存在很大的差异。瑞巴派特球状晶体的溶出速率高于针状晶体。结论瑞巴派特球状晶体是新晶型,它与针状晶体的晶型不同并且二者的溶出速率也存在明显差异。     

漫反射FT-IR和单晶XRD法研究盐酸林可霉素多晶型

目的：研究盐酸林可霉素2种晶型晶体结构中不同分子构象对其漫反射红外光谱行为的影响。方法：单晶X射线衍射法、傅立叶变换漫反射红外光谱法。结果：盐酸林可霉素2种晶型分属不同晶系及空间群。它们在晶胞中的分子内、分子间氢键与分子构象不同，从而造成其漫反射红外光谱行为的显著差别。结论：可用傅立叶变换红外漫反射光谱法鉴别盐酸林可霉素2种晶型。     

基于热分析技术的替格瑞洛晶型Ⅱ热性能研究

目的:对替格瑞洛晶型Ⅱ的热性能进行分析与研究。方法:通过差示扫描量热法和热台显微镜分析替格瑞洛晶型Ⅱ的热性能，并结合粉末X射线衍射法和光学显微镜分析替格瑞洛晶型Ⅱ的晶型及晶习特征与热性能的关系。结果:替格瑞洛晶型Ⅱ存在不同长径比的特征晶习，在粉末X射线衍射图上表现为特征峰相对强度的变化。替格瑞洛晶型Ⅱ在熔融过程中存在熔融转晶现象，晶习特征、粒径大小及分布，以及差示扫描量热仪的升温速率对其熔融转晶程度有较大影响。在粉末X射线衍射图谱等其它表征结果证实为替格瑞洛晶型Ⅱ的情况下，其差示扫描量热图谱上出现双峰现象为熔融转晶引起而非混晶造成。结论:通过对替格瑞洛晶型Ⅱ的热性能研究，为其差示扫描量热图谱有的呈现双峰有的呈现单峰的现象提供了合理的解释，为替格瑞洛原料药的质量控制提供更多的信息。     

Solid-state studies on the hemihydrate and the anhydrous forms of flunisolide

Flunisolide exists in at least two different anhydrous crystalline forms (I and II) and in a hemihydrate form with distinctly different physico-chemical properties. Modification II and the hemihydrate form are the commercial products. Form I was obtained by heating all other forms above 230 degrees C. The different crystalline forms of flunisolide were investigated by FTIR spectroscopy, X-ray powder diffractometry, differential scanning calorimetry (DSC), thermogravimetric analysis and thermomicroscopy both coupled with FTIR spectroscopy (TG-FTIR and FTIR thermomicroscopy). The three forms were easily differentiated by their IR spectra, X-ray powder diffraction patterns and thermal behaviour. Their stability was investigated under different experimental conditions to verify the tendency to solid solid transition and to study the existence range of the three forms. The relationship among the two anhydrous polymorphs and the hemihydrate form and their equilibrium solubilities in water at 20 degrees C were also investigated.     

磺胺甲噁唑的晶型转变研究

采用X线粉末衍射、差示扫描量热分析、热重量分析和红外光谱等分析手段,验证了磺胺甲噁唑存在两种晶型,即稳定型晶体(Ⅰ型)和亚稳定型晶体(Ⅱ型)。在一定的温度下Ⅱ型会转变为Ⅰ型,Ⅰ型在熔融状态下,骤冷又会转变成Ⅱ型。在水溶液中重结晶,只要控制冷却和结晶速度,可选择地制得Ⅰ型或Ⅱ型。     

Different crystal morphologies arising from different preparation methods of a same polymorphic form may result in different properties of the final materials: the case of diclofenac sodium trihydrate

Diclofenac sodium is a nonsteroidal anti-inflammatory drug widely used in painful and inflammatory diseases. It can exist in different hydrate phases. Recently the physico-chemical and pharmaceutical properties of a trihydrate form, named DSH3 were reported by the same authors. This short communication discusses how samples of a same polymorphic form can display dissimilar analytical signatures when obtained by different routes. Data from hot-stage microscopy, FT-IR spectroscopy, X-ray powder diffraction (XRDP) and thermal analysis were used to characterise the DSH3 samples prepared by different methods. Through the case study of diclofenac sodium, this work highlights how the method used to prepare a specific crystal modification can generate samples with different morphologies and therefore different properties and physical stability.     

Hydrate modifications of the non-steroidal anti-inflammatory drug diclofenac sodium: Solid-state characterisation of a trihydrate form

Diclofenac sodium is a non-steroidal anti-inflammatory drug widely used in painful and inflammatory diseases. It can exist in different hydrate phases. By exposure to different conditions of temperature and relative humidity can be isolated a trihydrate form never described in literature. The methods of preparation of the trihydrate form (named DSH3) were described and its physico-chemical properties were investigated. Data from FTIR spectroscopy, X-ray powder diffraction and thermal analysis were used for identification and characterisation of DSH3 in comparison with the anhydrous form (DS, the commercial form) and the hydrate form DSH (obtained by exposure of DS to relative humidity even below 60% and already described and characterised in a previous article of the same authors). Intrinsic dissolution studies were performed to compare the pharmaceutical properties of DS and DSH with DSH3, since this form was accidentally found on the Italian market as active pharmaceutical ingredient (API). This work stresses the importance of assessing the correct crystalline form also in API of well-established use to guarantee quality, safety and efficacy of the final dosage form. Furthermore, this study suggests that isomorphic hydrate forms with a different dislocation of water within the crystal structures can exist.     

Characterization and compaction behaviour of nimesulide crystal forms

Nimesulide is a typical nonsteroidal anti-inflammatory drug (NSAID), widely used in solid oral formulations. By crystallizing nimesulide from an ethanol solution a crystalline form was obtained, different from the reference sample, as confirmed by X-ray powder diffraction (XRPD), Differential Scanning Calorimetry (DSC) and solid cross polarization-magic angle spinning ((13)C-CPMAS) NMR. Moreover, when crystallized from dioxane nimesulide forms a solvate. The solvate was characterized by XRPD, IR-spectrometry, DSC, thermo-gravimetric analysis (TGA) and by (13)C-CPMAS NMR. In particular, through this technique, the presence of several conformational isomers was demonstrated. In addition to the physico-chemical characterization, the technological properties of nimesulide, namely densification and tableting, were evaluated. Contrarily to the other forms that are affected by capping phenomena at increasing compression pressures, the form obtained by desolvation of dioxane solvate has positive effect on tableting properties, increasing both compressibility and tabletability of nimesulide.     

Quantification of crystalline forms in active pharmaceutical ingredient and tablets by X-ray powder diffraction

A Merck development compound was known to exist in several polymorphic forms, hydrates and solvates. The polymorphic forms were characterized and the most thermodynamically stable form at room temperature was identified and taken into development. During routine stability analysis it became apparent that the crystalline form of the compound was converting from one form to another in tablets that were stored at 40 degrees C/75% relative humidity in open containers. This form conversion did not occur when the active pharmaceutical ingredient (API) alone was stored under these conditions. This paper describes the development and application of an X-ray powder diffraction method for the determination of the relative content of the two crystalline forms in API and within the final formulation. Results of monitoring the crystalline form conversion are reported and a possible mechanism of conversion is postulated.     

Development of novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability

To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction. The dissolution, bioavailability in rats and stability of solid dispersions were evaluated. Unlike conventional solid dispersion system, the itraconazole-loaded solid dispersion with relatively rough surface did not change crystalline form of drug. Our DSC and powder X-ray diffraction results suggested that this solid dispersion was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer of 10/2/0.5 gave maximum drug solubility of about 20 μg/mL. It did not change the crystalline form of drug for at least 6 months, indicating that it was physically stable. It gave higher AUC, C_max and T_max compared to itraconazole powder and similar values to the commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, it would be useful to deliver a poorly water-soluble itraconazole without crystalline change with improved bioavailability.     

羟喜树碱磷脂复合物理化性质的研究

目的研究羟喜树碱磷脂复合物的理化性质。方法用溶剂法制备羟喜树碱磷脂复合物,测定其在水中的溶解度和分散性,以差示扫描量热法研究其热力学性质,以X-射线衍射法研究羟喜树碱在磷脂中的存在状态。结果复合物中羟喜树碱在水中的溶解度显著增大,水中很容易分散形成纳米粒。DSC图谱表明复合物是不同于羟喜树碱、磷脂以及二者物理混合物的新物相。X-射线衍射表明在复合物中羟喜树碱与磷脂作用以无定形形态存在。结论羟喜树碱与磷脂形成复合物后,其理化性质发生明显变化。